SAVE: Single-Administration Vaccine Enhancement

Vaccination is one of the most effective and economic ways of fighting infectious diseases. To provide long-lasting immunity, well-timed booster shots are indispensable. Providing the necessary booster shots at the required times presents a large challenge, in humans as well as in wildlife and livestock vaccinations.
In this project we will use 3D printing with newly developed biomaterials as a solution for the delayed release of vaccine booster shots. Tubular capsules will be prepared that are inserted under the skin together with the first injection The capsule contains the vaccine as well as a sugar solution. The sugar will attract water inflow through the capsule wall by osmosis, leading to pressure build-up and eventually bursting of the capsule, and delivery of the vaccine booster. By carefully tailoring the material properties and capsule design, we aim to achieve release at the desired time-point, without needing any intervention. This will omit the need for a second visit to the doctor or a second visit from the vet; it will even allow to vaccinate wildlife without having to recapture the animals to give them their booster shots.
In previous work, we proved this principle of osmosis-mediated delivery, from polymer capsules prepared by a simple dip coating technique. In this project we take the next step: preparing these capsules using stereolithography fabrication, a form of 3D printing, to achieve a more precise, reproducible and reliable release. Once we have demonstrated the ability to tune the release, we will apply our technology to deliver booster shots against tuberculosis in cattle. Before using the capsules in animals, we will show that the capsules are safe to use by culturing cells on them in a dish, and test for toxicity and inflammation.
We believe our new technology can help solve many problems, including the timely delay of vaccines, antibiotics, chemotherapeutics and other drugs, both in animals and humans. In this project we will take the first step by developing and testing the capsules, and applying them to fight tuberculosis in cattle.

It is well recognised that boosting of vaccine-induced immunity is required for long-term protection. A major challenge is to provide the necessary booster shots at the required intervals, particularly for non-housed animals. In this project, we will develop a materials technology platform that, contrary to existing devices, will ensure immediate and complete release of a vaccine booster at the optimal time point, from a capsule that is inserted under the skin at the time of the first vaccination.
To this end, we propose an implantable polymer capsule that contains the vaccine together with an osmolyte. The polymer will be selectively permeable to water so that the osmolyte drives the swelling of the capsule over time, ultimately resulting in rupture of the capsule and instant release of the payload. Unique to single administration vaccination strategies, our approach does not require co-processing of biomaterials and the active compound. This gives ample freedom for tuning the delay time and other properties of the device, enables the use of existing vaccine formulations, which will not be subjected to harsh processing conditions, and will be incorporated quantitatively.
Polymers with tailored water permeability will be synthesised and employed with stereolithography, a 3D printing technique, to prepare the capsules. The reproducibility and effectiveness of the release will be studied both in vitro and in vivo, and the device and its degradation products will be tested for toxicity and tissue response. While holding potential for a plethora of diseases, we will focus initially on bovine tuberculosis, a significant problem in UK cattle herds. The causative agent is also an important origin of human disease worldwide. If successful, this approach could save cost by eliminating the need to perform repeated vaccinations, as well as enable providing timely booster shots for animals without the need to recapture the animal or keep it in captivity.

The following specific impacts are associated with this project:
1. Paving the way for commercialisation and manufacture of the device. Generating an interest for the technology with pharmaceutical companies should not commence only after the technology has been fully developed, but will start during the project in liaison with the knowledge transfer bodies at both HWU and The Roslin Institute. Initial market research and cost analysis of this technology vs. current options will be performed by a professional partner, to establish market potential of the technique under development.
2. Preparing vets, farmers and policy makers to facilitate the uptake of the upcoming new technology. We will gauge current opinions via survey, and develop an understanding and appreciation of the novel technology with stakeholders through targeted engagement including the Royal Highland Show, audience-targeted Open Days at the Roslin Innovation Centre, and veterinary and farming press. We have already initiated discussions with the Veterinary Medicines Directorate, part of the Department for Environment, Food & Rural Affairs (DEFRA), and the Medicines and Healthcare products Regulatory Agency (MHRA) to pre-empt potential obstacles on the route towards regulatory approvals and final application.
3. Expanding our collaborative network to start exploiting the wide range of potential applications, with a particular focus on Official Development Aid. As tuberculosis and vaccine delivery in general fit the Global Challenges particularly well, the collaborative network will be expanded through networking hubs to find overseas partners for follow-up projects, in which the novel technology will be tailored to regional needs and limitations.
4. Exploiting the opportunity this project brings to give the general public an appreciation for multidisciplinary research. Combining engineering and health, this project is ideal for showcasing multidisciplinary research, which will be performed through the Edinburgh Fringe Festival (Cabaret of Dangerous Ideas), the Edinburgh International Science festival and the Royal Highlands Show.